NEAT1 contributes to breast cancer progression through modulating miR-448 and ZEB1.

Abstract

Breast cancer is a kind of common female cancers. Increasing evidence has exhibited that lncRNAs exert a crucial role in breast cancer. So far, the mechanism of lncRNAs in breast cancer is still not well established. In our current study, we focused on the biological role of lncRNA Nuclear Enriched Abundant Transcript 1 (NEAT1) in breast cancer. We observed that NEAT1 levels were significantly increased in human breast cancer cells including MCF-7, MDA-MB-453, MDA-MB-231, and SKBR3 cells compared to normal mammary epithelial cells MCF-10A while miR-448 was decreased. We found that downregulation of NEAT1 was able to inhibit the growth of breast cancer cells and miR-448 mimic exerted the similar function. Bioinformatics analysis and dual luciferase reporter assays confirmed the negative correlation between NEAT1 and miR-448 in vitro. In addition, ZEB1 was predicted as a novel mRNA target of miR-448. Overexpression of NEAT1 can induce breast cancer cell growth, migration, and invasion by inhibiting miR-448 and upregulating ZEB1. It was demonstrated that NEAT1 can increase ZEB1 levels while miR-448 mimic can repress ZEB1. It was speculated in our study that NEAT1 can serve as a competing endogenous lncRNA (ceRNA) to modulate ZEB1 by sponging miR-448 in breast cancer. To conclude, we uncovered that NEAT1 participated in breast cancer progression by regulating miR-448 and ZEB1. NEAT1 can be provided as a vital biomarker in breast cancer diagnosis and treatment therapy.